Sulforaphane Induces miR135b-5p and Its Target Gene, RASAL2, thereby Inhibiting the Progression of Pancreatic Cancer

Yin, Libo; Xiao, Xi; Georgikou, Christina; Luo, Yiqiao; Liu, Li; Gladkich, Jury; Groß, Wolfgang; Herr, Ingrid

doi:10.1016/j.omto.2019.03.011

Cited by 31 publications

(18 citation statements)

References 33 publications

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“…Questions remain regarding RASAL2 deregulation in tumour tissues. Interestingly, recent studies revealed that RASAL2 expression is controlled by specific miRNAs, including miR‐136, miR‐135b‐5p, and miR‐203 . Considering that RASAL2 is overexpressed in colorectal cancer, we aimed to determine whether it is regulated by specific miRNAs.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA‐876‐5p represses the cell proliferation and invasion of colorectal cancer through suppressing YAP signalling via targeting RASAL2

Ren

Zhang

Feng

et al. 2020

Clin Exp Pharma Physio

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Aberrant expression of microRNA‐876‐5p (miR‐876‐5p) is implicated in the progression of multiple human cancers. However, the potential role of miR‐876‐5p in colorectal cancer remains poorly understood. The purpose of the current study was to investigate the potential role of miR‐876‐5p in colorectal cancer. miR‐876‐5p expression was significantly downregulated in colorectal cancer tissues and cell lines compared with normal controls. Gain‐of‐function assays revealed that miR‐876‐5p overexpression effectively repressed the malignant behaviours of colorectal cancer cells, including cell proliferation, colony formation, and invasion. Bioinformatics analysis predicted that RAS protein activator like 2 (RASAL2), a potential oncogene for colorectal cancer, is a putative miR‐876‐5p target gene. A luciferase reporter assay confirmed that miR‐876‐5p directly binds to the 3′‐untranslated region (UTR) of RASAL2. Furthermore, both RASAL2 messenger RNA (mRNA) and protein expression were negatively modulated by miR‐876‐5p in colorectal cancer cells. Notably, there was an inverse correlation between miR‐876‐5p and RASAL2 expression in colorectal cancer tissue specimens. Moreover, miR‐876‐5p was involved in regulating the activation of Yes‐associated protein (YAP) signalling through inhibiting RASAL2. However, the miR‐876‐5p‐mediated antitumour effect on colorectal cancer cells was partially reversed by restoring RASAL2 expression. Notably, miR‐876‐5p upregulation impeded the tumour growth of colorectal cancer cells in vivo in nude mice. Overall, these results demonstrated that miR‐876‐5p exerts an antitumour function in colorectal cancer by targeting RASAL2 to suppress YAP signalling activation. These findings highlight the importance of the miR‐876‐5p/RASAL2/YAP axis in colorectal cancer progression and suggest that miR‐876‐5p is a potential therapeutic target for treating colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

“…Interestingly, recent studies revealed that RASAL2 expression is controlled by specific miRNAs, including miR-136, miR-135b-5p, and miR-203. 17,40,41 Considering that RASAL2 is overexpressed in colorectal cancer, we aimed to determine whether it is regulated by specific miRNAs. Notably, we identified RASAL2 as a miR-876-5p target gene.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐876‐5p represses the cell proliferation and invasion of colorectal cancer through suppressing YAP signalling via targeting RASAL2

Ren

Zhang

Feng

et al. 2020

Clin Exp Pharma Physio

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“…In terms of antitumor activity, sulforaphane has shown great potential for treatment of cancers such as bladder cancer (Xia, Kang, Jung, Zhang, & Lian, ), colon cancer (Darkwa, Burkhardt, & Tsuji, ), triple negative breast cancer (Jensen, Slattery, Housley, & Hansen, ), pancreatic cancer (Yin et al, ), prostate cancer (Traka et al, ), and non‐small cell lung cancer (Zheng et al, ). Although high numbers of studies have investigated the antitumor activity of sulforaphane, there is a need for a precise review to describe the mechanism of antitumor activity of sulforaphane.…”

Section: Significant Properties Of Sulforaphanementioning

confidence: 99%

“…In terms of antitumor activity, sulforaphane has shown great potential for treatment of cancers such as bladder cancer (Xia, Kang, Jung, Zhang, & Lian, 2019), colon cancer (Darkwa, Burkhardt, & Tsuji, 2019), triple negative breast cancer (Jensen, Slattery, Housley, & Hansen, 2019), pancreatic cancer (Yin et al, 2019), prostate cancer (Traka et al, 2019), and non-small cell lung cancer .…”

Section: Significant Properties Of Sulforaphanementioning

confidence: 99%

MicroRNAs as novel targets of sulforaphane in cancer therapy: The beginning of a new tale?

Rafiei

Ashrafizadeh

Ahmadi

2020

Phytotherapy Research

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Effective management and treatment of cancer depend on developing novel antitumor drugs with the capability of targeting various molecular pathways. Identification and subsequent targeting of these pathways are of importance in cancer therapy. MicroRNAs (miRNAs) are small noncoding RNA molecules responsible for post‐transcriptional regulation of genes. Notably, miRNAs participate in a number of biological processes such as proliferation, apoptosis, differentiation, and cell cycle regulation. So, any impairment in the expression and function of miRNAs is associated with development of disorders, particularly cancer. Naturally occurring nutraceutical compounds have attracted much attention due to their great antitumor activity. Among them, sulforaphane isolated from Brassica oleracea (broccoli) is of interest due to its therapeutic and biological activities such as antidiabetic, antioxidant, anti‐inflammatory, hepatoprotection, and cardiprotection. Sulforaphane has demonstrated great antitumor activity and is able to significantly inhibit proliferation, viability, migration, malignancy, and epithelial‐to‐mesenchymal transition of cancer cells. These antitumor effects have widely been investigated, and it appears that there is a need for a precise review to demonstrate the molecular pathway that sulforaphane follows to exert its antitumor activity. At the present review, we focus on the modulatory impact of sulforaphane on miRNAs and exhibit that how various miRNAs in different cancers are regulated by sulforaphane.

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“…Moreover, growth-inhibitory effects for sulforaphane in head, neck and prostate cancer 583 cells have been reported (Singh et al 2005;Gupta et al 2015) and PEITC has been associated 584 with prevention of the growth of oral cancer cell lines (Chen et al 2012). Currently, their 585 potential effects on different cancer types is a matter of extensive exploration (Castro et al 586 2019;Mitsiogianni et al 2019;Upadhyaya, Liu & Dey 2019;Yin et al 2019). Sulphoraphane 587 has also been proposed as a potential therapy for precluding vascular complications in diabetes 588 (Yamagishi & Matsui 2016).…”

mentioning

confidence: 99%

Growth under high light and elevated temperature affects metabolic responses and accumulation of health-promoting metabolites in kale varieties

Alegre

Pascual

Trotta

et al. 2019

Preprint

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19Plants are highly sensitive to changes in the light environment and respond to alternating light 20 conditions by coordinated adjustments in foliar gene expression and metabolism. Here we 21 assessed how long-term growth under high irradiance and elevated temperature, a scenario 22 increasingly associated with the climate change, affects foliar chemical composition of 23 Brassicaceous plants. Transcript profiling of Arabidopsis suggested up-regulation of 24 phenylpropanoid metabolism and down-regulation of processes related to biotic stress 25 resistance and indole glucosinolates (GSL). These observations prompted metabolite profiling 26 of purple (Black Magic) and pale green (Half Tall) varieties of kale, an economically important 27 crop species. Long-term acclimation to high light and elevated temperature resulted in reduced 28 levels of 4-methoxy-indol-3-yl-methyl GSL in both kale varieties. The total levels of aliphatic 29 GSLs increased under these conditions, although the profiles of individual GSL structures 30 showed cultivar-dependent differences. Black Magic became rich in 4-methylsulfinylbutyl 31 GSL and 2-phenylethyl GSL, which have health-promoting effects in human diet. Additionally, 32 the purple pigmentation of Black Magic became intensified due to increased accumulation 33 anthocyanins, especially derivatives of cyanidin. These findings demonstrate that the 34 potentially stressful combination of high light and elevated temperature can have beneficial 35 effects on the accumulation of health-promoting metabolites in leafy vegetables. 36 37 Key words 38 Arabidopsis, Brassica, high light acclimation, transcriptome, metabolite profiling, 39 glucosinolate, anthocyanins 40 41 42 43 3 Acknowledgements 44

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Sulforaphane Induces miR135b-5p and Its Target Gene, RASAL2, thereby Inhibiting the Progression of Pancreatic Cancer

Cited by 31 publications

References 33 publications

MicroRNA‐876‐5p represses the cell proliferation and invasion of colorectal cancer through suppressing YAP signalling via targeting RASAL2

MicroRNA‐876‐5p represses the cell proliferation and invasion of colorectal cancer through suppressing YAP signalling via targeting RASAL2

MicroRNAs as novel targets of sulforaphane in cancer therapy: The beginning of a new tale?

Growth under high light and elevated temperature affects metabolic responses and accumulation of health-promoting metabolites in kale varieties

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